Endomorphins and related opioid peptides
by
Okada Y, Tsuda Y, Bryant SD, Lazarus LH.
Faculty of Pharmaceutical Sciences,
High Technology Research Center,
Kobe Gakuin University, Kobe 651-2180, Japan.
Vitam Horm 2002;65:257-79
ABSTRACTOpioid peptides and their G-protein-coupled receptors (delta, kappa, mu) are located in the central nervous system and peripheral tissues. The opioid system has been studied to determine the intrinsic mechanism of modulation of pain and to develop uniquely effective pain-control substances with minimal abuse potential and side effects. Two types of endogenous opioid peptides exist, one containing Try-Gly-Gly-Phe as the message domain (enkephalins, endorphins, dynorphins) and the other containing the Tyr-Pro-Phe/Trp sequence (endomorphins-1 and -2). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), which has high mu receptor affinity (Ki = 0.36 nM) and remarkable selectivity (4000- and 15,000-fold preference over the delta and kappa receptors, respectively), was isolated from bovine and human brain. In addition, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), isolated from the same sources, exhibited high mu receptor affinity (Ki = 0.69 nM) and very high selectivity (13,000- and 7500-fold preference relative to delta and kappa receptors, respectively). Both opioids bind to mu-opioid receptors, thereby activating G-proteins, resulting in regulation of gastrointestinal motility, manifestation of antinociception, and effects on the vascular systems and memory. To develop novel analgesics with less addictive properties, evaluation of the structure-activity relationships of the endomorphins led to the design of more potent and stable analgesics. Opioidmimetics and opioid peptides containing the amino acid sequence of the message domain of endomorphins, Tyr-Pro-Phe/Trp, could exhibit unique binding activity and lead to the development of new therapeutic drugs for controlling pain.Pain
LAAM
Tolerance
Sugar junkies
Knockout mice
Opium timeline
Opioid receptors
Endomorphins 1 and 2
Endomorphins and the mouse
The rewards of endomorphin 1
Endomorphins and rodent brains
Adenylyl cyclase superactivation
The degradation of endomorphins
Endomorphins 1 and 2 as antidepressants
Endomorphins and the mu-opioid receptor
Morphine: a mood-brightening smart-drug?
Opioids, depression and learned helplessness
Endomorphin-1, accumbal dopamine and the mu-opioid receptor
A peripherally administered endomorphin-1 analogue offers pain relief
and further reading
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